| Title: |
Structural basis for membrane targeting and secretion of legionella SidE ubiquitin ligases |
| Authors: |
Misra, Mohit; Mukherjee, Rukmini; Bhattacharya, Anshu; Weng, Tsai-Hsuan; Li, Chuang; Chen, Wenbo; van Ek, Larissa; Mohammed, Ahmed; Cristiani, Alberto; Liu, Yaobin; Pomirska, Julia; Vidov, Adela; Grewe, Diana; van der Heden van Noort, Gerbrand; Hummer, Gerhard; Gavin, Anne-Claude; Safarian, Schara; Luo, Zhao-Qing; Bhaskara, Ramachandra; Svergun, Dmitri; Kudryashev, Misha; Dikic, Ivan |
| Publisher Information: |
Research Square |
| Publication Year: |
2025 |
| Collection: |
Max-Delbrueck-Center for Molecular Medicine, Berlin: MDC Repository |
| Subject Terms: |
Cancer Research; Topic 2: Molecular Processes and Therapies |
| Description: |
SidE family effectors from Legionella pneumophila catalyze serine ubiquitination of host proteins via phospho-ribose (PR) linkages, disrupting host compartments, facilitating the formation of Legionella-containing vacuoles (LCVs) and blocking xenophagy. Upon infection, SidE proteins are injected into the cytosol and recruited to host membranes. Here we present structural and functional insights into a previously uncharacterized C-terminal domain (CTD) of SidE effectors. The crystal structure reveals a banana-shape resembling eukaryotic BAR-domain dimers, with an amphipathic helix and electropositive patch mediating membrane association. Membrane targeting to ER and Golgi confers substrate specificity for PR-ubiquitination. We further show that the CTD binds the IcmS-IcmW-DotL complex, acting as a secretion signal for the Type IV secretion system. Our findings establish membrane localization and secretion as critical determinants of SidE effector function during Legionella infection. |
| Document Type: |
report |
| File Description: |
application/pdf; other |
| Language: |
English |
| Relation: |
https://edoc.mdc-berlin.de/id/eprint/26021/1/26021oa.pdf; https://edoc.mdc-berlin.de/id/eprint/26021/2/26021suppl.xlsx; Structural basis for membrane targeting and secretion of legionella SidE ubiquitin ligases. Misra, Mohit, Mukherjee, Rukmini, Bhattacharya, Anshu, Weng, Tsai-Hsuan, Li, Chuang, Chen, Wenbo, van Ek, Larissa, Mohammed, Ahmed, Cristiani, Alberto, Liu, Yaobin, Pomirska, Julia, Vidov, Adela, Grewe, Diana, van der Heden van Noort, Gerbrand, Hummer, Gerhard, Gavin, Anne-Claude, Safarian, Schara, Luo, Zhao-Qing, Bhaskara, Ramachandra, Svergun, Dmitri, Kudryashev, Misha and Dikic, Ivan Research Square : rs.3.rs-6524297/v1. 12 May 2025; ResearchSquare:rs.3.rs-6524297/v1; https://doi.org/10.21203/rs.3.rs-6524297/v1 |
| DOI: |
10.21203/rs.3.rs-6524297/v1 |
| Availability: |
https://edoc.mdc-berlin.de/id/eprint/26021/; https://edoc.mdc-berlin.de/26021/; https://doi.org/10.21203/rs.3.rs-6524297/v1 |
| Rights: |
cc_by_4 |
| Accession Number: |
edsbas.7EBBEECE |
| Database: |
BASE |